Pharmacokinetic/Pharmacodynamic (PK/PD) Study Evaluating Pegfilgrastim Hospira Compared to Neulasta (Amgen) in Healthy Volunteers

A Phase I, Randomized, Single Dose, Crossover Study Evaluating the Pharmacokinetics and Pharmacodynamics of Pegfilgrastim Hospira Compared to Neulasta (Amgen) Following Subcutaneous Administration to Healthy Volunteers

This study compared the pharmacokinetics, pharmacodynamics and the safety of Pegfilgrastim Hospira and Neulasta® following a single dose of 6 mg of each product administered subcutaneously in Treatment Periods 1 and 2, respectively, in healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Pegfilgrastim Hospira; Drug: Neulasta (Amgen)

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Edinburgh, United Kingdom, EH14 4AP
    • Quotient Clinical LTD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male or female subjects, 18-55 years inclusive.
• Written informed consent given
• Willing and able to comply with the requirements of the protocol and be available for the planned duration of the study.
• Body Mass Index (BMI) between 19 and 30 kg/m2 inclusive and weight not <50 kg or >100 kg.
• Female subjects who are using an effective method of contraception, or are surgically sterile.
• Non-smokers or ex-smokers who have not smoked within the previous 12 months.

Exclusion Criteria:

• Hypersensitivity to the Investigational medicinal product (IMP) or its constituents and/or hypersensitivity to E. Coli derived proteins, and/or previous exposure to the IMP.
• History or presence of any clinically significant findings that, in the opinion of the Investigator, would preclude inclusion in the study.
• History or presence of any clinically significant gastrointestinal pathology or symptoms, liver or kidney disease, or any other condition that might interfere with the absorption, distribution, metabolism or excretion of the drug.
• Any clinically significant laboratory findings, including any ANC, platelet or haemoglobin result outside the reference range of the local laboratory.
• Abnormal vital signs or abnormal 12-lead electrocardiogram (ECG) results, as judged by the Investigator to be clinically significant.
• Females, pregnant or lactating, or planning to become pregnant during the time the subject is on study.
• Subjects with a history of pulmonary infiltrate or pneumonia in the previous 6 months from the date of the screening visit.
• Hereditary fructose intolerance.
• Participation in any other clinical trial using a investigational product or device, within the previous 12 weeks from the date of the screening visit.
• Positive result for human immunodeficiency virus (HIV) and/or hepatitis B and C tests.
• Evidence of, or treatment for, drug or alcohol abuse within one year from date of screening visit.
• Blood donation >=500 mL in the previous 12 weeks from the date of the screening visit.
• Use of any prescription medication (excluding hormonal contraceptives) within 14 days prior to date of the screening visit.
• Receipt of over-the-counter medicines which have not yet cleared from the body (five half-lives must have passed for the medicine to be considered to have cleared from the body). Vitamins, minerals and nutritional supplements may be taken at the discretion of the Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group 1	Drug: Pegfilgrastim Hospira; Subjects in both treatment groups will have safety assessments and will be followed for all adverse and serious adverse events.
Active Comparator: Treatment Group 2	Drug: Neulasta (Amgen); Subjects in both treatment groups will have safety assessments and will be followed for all adverse and serious adverse events.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve from time 0 extrapolated to infinity (AUC0-∞) for serum Pegfilgrastim (PEG-GCSF)		Treatment Periods 1 and 2: Pre-dose (-15 min) and post-dose 1, 2, 4, 6, 8, 10, 16, 24±2, 48±2, 72±2, 96±2, 120±2, 144±2, 168±2, 192±2, 216±2, 240±2, 264±2, 288±2 hours or early discontinuation.
Area under the curve from time 0 to the last time point (AUC0-t) for serum Pegfilgrastim (PEG-GCSF)	AUC0-t will be used as a primary parameter only if AUC0-∞ cannot be calculated for all subjects in the pharmacokinetic population.	Treatment Periods 1 and 2: Pre-dose (-15 min) and post-dose 1, 2, 4, 6, 8, 10, 16, 24±2, 48±2, 72±2, 96±2, 120±2, 144±2, 168±2, 192±2, 216±2, 240±2, 264±2, 288±2 hours or early discontinuation.
Pharmacodynamics: Maximum change from baseline in absolute neutrophil count (ANC); ANC_Cmax		Screening, Day -1, Treatment Periods 1 & 2: Pre-dose (-60 min, -30 min, 0 min), Post dose (12 hr, 24±2, 48±2, 72±2, 96±2, 120±2, 144±2, 168±2, 192±2, 216±2, 240±2, 264±2, 288±2)

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum concentration (Cmax) for serum Pegfilgrastim (PEG-GCSF)	Treatment Periods 1 and 2: Pre-dose (-15 min) and post-dose 1, 2, 4, 6, 8, 10, 16, 24±2, 48±2, 72±2, 96±2, 120±2, 144±2, 168±2, 192±2, 216±2, 240±2, 264±2, 288±2 hours or early discontinuation.
Time to maximum concentration (Tmax) for serum Pegfilgrastim (PEG-GCSF)	Treatment Periods 1 and 2: Pre-dose (-15 min) and post-dose 1, 2, 4, 6, 8, 10, 16, 24±2, 48±2, 72±2, 96±2, 120±2, 144±2, 168±2, 192±2, 216±2, 240±2, 264±2, 288±2 hours or early discontinuation.
Terminal elimination rate constant (λz) for serum Pegfilgrastim (PEG-GCSF)	Treatment Periods 1 and 2: Pre-dose (-15 min) and post-dose 1, 2, 4, 6, 8, 10, 16, 24±2, 48±2, 72±2, 96±2, 120±2, 144±2, 168±2, 192±2, 216±2, 240±2, 264±2, 288±2 hours or early discontinuation.
Half-life (T½) for serum Pegfilgrastim (PEG-GCSF)	Treatment Periods 1 and 2: Pre-dose (-15 min) and post-dose 1, 2, 4, 6, 8, 10, 16, 24±2, 48±2, 72±2, 96±2, 120±2, 144±2, 168±2, 192±2, 216±2, 240±2, 264±2, 288±2 hours or early discontinuation.
Area under the curve above baseline of ANC [ANC_AUC(0-tlast)]	Screening, Day -1, Treatment Periods 1 & 2: Pre-dose (-60 min, -30 min, 0 min), Post dose (12 hr, 24±2, 48±2, 72±2, 96±2, 120±2, 144±2, 168±2, 192±2, 216±2, 240±2, 264±2, 288±2)
Time of maximum change from baseline for ANC in days (ANC_Tmax)	Screening, Day -1, Treatment Periods 1 & 2: Pre-dose (-60 min, -30 min, 0 min), Post dose (12 hr, 24±2, 48±2, 72±2, 96±2, 120±2, 144±2, 168±2, 192±2, 216±2, 240±2, 264±2, 288±2)
Maximum change from baseline in CD34+ count (CD34+_Cmax)	Day -1, Treatment Periods 1 & 2: Post dose (12 hr, 24±2, 48±2, 72±2, 96±2, 120±2, 144±2, 168±2, 192±2, 216±2, 240±2)
Time of maximum change from baseline for CD34+ count in days (CD34+_Tmax)	Day -1, Treatment Periods 1 & 2: Post dose (12 hr, 24±2, 48±2, 72±2, 96±2, 120±2, 144±2, 168±2, 192±2, 216±2, 240±2)

Collaborators and Investigators

• Sponsor: Hospira, now a wholly owned subsidiary of Pfizer

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: July 10, 2009
• First Submitted That Met QC Criteria: July 10, 2009
• First Posted (Estimate): July 14, 2009

Study Record Updates

• Last Update Posted (Actual): March 20, 2017
• Last Update Submitted That Met QC Criteria: March 16, 2017
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: Healthy volunteers
• Other Study ID Numbers: PEG-09-01; EudraCT Number 2009-101433-42